BMP-2 is a protein that belongs to the superfamily called transforming growth factor beta (TGF-beta). BMP-2 is known to induce the formation of bone and cartilage. For example, BMP-2 has been used to promote bone repair by surgically implanting a collagen matrix combined with the protein. BMP-2 is loaded into an absorbable collagen sponge as an aqueous suspension. The BMP-2 non-specifically associates with the collagen. However, due to the low binding capacity of the collagen fibrils toward BMP-2, and vice versa, BMP-2 can leak out of the collagen matrix. This leakage of BMP-2 from the collagen sponge causes undesirable exuberant and/or ectopic bone formation at or near the implant site. Undesirable bone growth leads to further complications, resulting in additional corrective surgery or surgeries for the patient.
Therefore, there is a need for a controlled release device for BMP-2 to eliminate the problematic side effect of bone formation in undesired locations. Standard methods for preparing controlled release devices include the use of polymeric matrices, typically in the form of microspheres, rods, sheets or pellets, which are used to encapsulate the active agent. A variety of techniques are known by which active agents can be incorporated into polymer matrices. Examples include solvent evaporation, spray drying, emulsification, melt blending and simple physical mixing of particles of discrete size or shape. None of these approaches may be applied to incorporate peptides or proteins into the polymers due to the delicate nature of these molecules. Peptides and proteins are susceptible to denaturation by solvents, by emulsification, by heat and, in particular, by terminal sterilization.
Therefore, there is a need for a method of making a controlled release device for BMP-2, where the method does not denature or otherwise inactivate the activity of the protein. A controlled release device for BMP-2 is also desired which provides a localized, sustained release of the protein, and thus avoids undesired ectopic bone formation.